More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages.
U.S. Pat. No. 3,393,197, issued to Pachter and Matossian on July 16, 1968, discloses N-substituted-14-hydroxydihydronormorphines, including the N-cyclobutylmethyl derivative, commonly called nalbuphine: ##STR1## Pachter and Matossian and others, such as H. W. Elliott, et al., J. Med. (Basel), 1, 74-89 (1970); H. Blumberg, et al., Pharmacologist, 10, 189 (Fall 1968); P. Roberts, Drugs of the Future, 2, 613-5 (1977), discloses the use of nalbuphine as an analgesic for the control of moderate to severe pain.
U.S. Pat. No. 4,237,140, issued to J. R. Dudzinski on Dec. 2, 1980, describes an analgesic mixture of nalbuphine and acetaminophen. U.S. Pat. No. 4,282,215, issued to J. R. Dudzinski and W. K. Schmidt on Aug. 4, 1981, describes an analgesic mixture of nalbuphine and aspirin.
U.S. Pat. No. 3,752,826 issued to J. R. Carson discloses the synthesis and utility of 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetic acid, commonly called zomepirac: ##STR2## Additional information characterizing the analgesic properties of zomepirac are listed in New Drug Commentary, 8(5), May 1981.
Analgesic mixtures of zomepirac with acetaminophen are disclosed in U.S. Pat. No. 4,260,629, analgesic mixtures with butorphanol are disclosed in U.S. Pat. No. 4,322,427, and mixtures with aspirin or acetaminophen are disclosed in U.S. Pat. No. 4,132,788.